CA1181717A

CA1181717A - Electrochemical dehydrogenation of steroidal .delta. su3,5 xx enol ethers under basic conditions to provide steroidal .delta. su4,6 xx dienones

Info

Publication number: CA1181717A
Application number: CA000371301A
Authority: CA
Inventors: James R. Behling
Original assignee: GD Searle LLC
Current assignee: GD Searle LLC
Priority date: 1980-02-20
Filing date: 1981-02-19
Publication date: 1985-01-29
Also published as: FR2476094B1; JPS56135499A; US4270994A; DE3106162A1; AU6745681A; GB2070017A; FR2476094A1; GB2070017B

Abstract

ABSTRACT

An improved process for the preparation of steroidal .DELTA. 4,6 dienones by the electrochemical dehydrogena-tion of the corresponding .DELTA. 3,5 enol ethers under basic con-ditions, using a hlgh potential quinone catalyst, such as 2,3-dichloro-5,6-dicyano-benzoquinone, in a partially aqueous electrolyte solution.

Description

2/.1'1/~0 ~C-~e 2180 ELECTROCHEMICAL DEHYDROGENATION OF STEROIDAL
ENO~ ETHERS UNDER BASIC CONDITIONS TO
.PRO~I~E STEROID~L ~ DIENONES

Back~round of th Invention .
In view of the ~mportance o:E steroids as therapeutic agents, there has been considerable effort sPent in de~eloping improved processes for preparin~ various steroidal speçies.
One such development has centered on the dehydrogen-ation of steroidal ~ ' enol ethers with 2,3-dichloro-5,6~
10 dicyanobenzoquinone and similar reagents. See for example, Pradham et al., "The Dehydrogenation o Steroidal j3'sEnol Ethers with Dichlorodicyanobenzoquinone(DD~)~, J Oraan. Chem., 29, pp. 601~604~19S4~; Fried e~ al., Or~ Rcact~rs i~
Steroid Chemistry,Vol. 1, ~p. 30~-313(Van Nostrand Reinhold _ 15 Company, ~ew York, 1972~; and Walker et al. r "2,3-Dichloro-- 5,6-Dicyanobenzoquinone and Its Reactions", Chem. Rev., 67, ~p. 153-195(19~7).
Burn et al., Chemistry and IndustrY~p. 497tl966) ; reported the formation of 17-~-acetoxv-6-hydroxymethyl-3-20 methoxypregna-4,6-diene-20-one with 2,3-dichloro 5,6-dicyano-- benzoquinone(DD~) as the reaqent in aqueous acetone and su~aested extension o~ that reaction ko other 3~alkoxy-6-hydroxyme~hyl-4,5-dien-3-ones in the andros~ane~ l9-norandrostane, ~regnane and corticoid speci~s.
It has now been found that the ~ields can be improved and other advanka~es obtained bv the electroche~ical dehydrogen-.ation of the ~3' enol ethers with ~,3-dichlor~-5~6~dicyano-, benzoq~ino~e,or another s~itable high Potential ~uinone, in basic system. This process provides an une~pected increase in the yields obtai~ed by the chemical d~ydrog~atio~ of the prior art, has the further advantage of providing end prod~lct 5 of greater purity, is a cleanex reaction, is operable with catalytic or less than stoichiometric amounts of the quinone, and further allows for the regeneration and recovery of the catalyst when 2~3-dicloro-5 t 6-dicyanobenzoquinone or 2,3-dichloro-5,6-dicyanohydroquinone is employed. In both cases, 10 DDQ is recovered. The results obtained are ~articularly surprising since the quinones are base sensitive.
~ he regeneration and ~eco~ery of 2,3 dic~loro-5~5-dicyanobenzoquinone by the anodic oxidation of 2,3-dichloro-5,6-dicyanohydroquinone has been reported by Brinker et al.
Synthesis~ ~. 671~1975~. Howe~ert there has been no suqgestion o~ using the quinones in electrochemical d~ydrogenation of steroids. Other high potential quinonès useful in ~he practice of the present invention are disclosed by Jackman,"Hydrogenation-Dehydro~enation Reactions~, ~avances in ~rqanic Chemistr~, Vol 202, pp. 329-333(Interscience Publishers, Inc.~ New York,1~60)~
Summary The present inventiQn provîdes an im~roved process for the preparation of steroidal ~' dienones by the electro-chemical d~yc~c~ ~ ~o~ of th2 corresDonding ~ enol ethers 25under basic conditionsl using less ther. stochiometric amounts of a high potential catalyst, such as 2,3-dichloro-5,6-dicyano-benzoquinone as a catalyst, in a partially aqueous electrolyte solution.
etailed ~escription of Pre~erred Embodiments The improved process o~ preparing steroidalQ ~dienones of the present invention comprises the electrochemical dehydro-genation ~f steroidal ~ enol ethers to their corresponding ~' dienones in h;gh yields8 The d~yc~c~en~-tion is accomplished by anodic oxidation using 2,3-dichloro-5,6-dicyanobenzoquinone, 35 2,3-dichloro-~,6-dicyanohydroquinone or another suitable high potential catalyst, as a catalytic electron carrier. Th~
reaction is carrird out under basic conditions in a partially aqueous electrolyte system as described in detail hereinbelow.
The process of the present invention can be carried out ei~her b~ batch method in a clivided or undivided cell, or in a continuous flow sys-tem. In the case of divided cells, sllitable cell dividers inlcude ion exchancJe membranes such as DuPo~t's ~fion~ pol~halogenated Teflon men~ranes or other suitabl- I~orous dividers,i.e., sintered tJlaSSI ccram:ics,etc.
i, * 'I'r,:lde Mclrk For purposes of illustration, the invention is des-cribed using a divided H cell having a carbon anode with a silver/silver nitrate reference electrode and a platinum cathode.
Generally speaking, th~ enol ether, catalys-t, solvent and base are placed in the anode compartment of a II cell along with a suitable reference electrode such as a sil-ver/silver nitrate electrode. The electrolyte solution is placed in the cathode chamber along with a suitable cathode such as a 6 cm x 2 cm platinum foil sheet. Sufficient cell voltage is applied such that current passes and the reac-tion proceeds for a period of time sufficient to complete the reaction, generally from about 2 to about 5 hours, and the dienone is recovered and isolated using standard methods.
The addition of a basifying agent, such as a soluble or partially soluble carbonate~ bicarbonate, oxide, hydro-xide and the like to the anolyte improves the effectiveness of the process as cloes agitation of the electrolyte solution.
The term "catalyst" refers to high potential quinones.
The preferred catalyst is 2,3-dichloro-5,6-dicyanobenzoqui-none. Other high potential catalysts can be employed in the practice of this invention. The term "high potential cata-lysts" includes 2,3-dichloro-5,6-dicyanobenzoquinone, 2,3-dichloro-5,6-dicyanohydroquinone, 3,3',5,5'-tetrachloro-4,4~-diphenoquinone, tetrachloro 1,2-benzoquinone and the like. Chloranil can also be employed under appropriate conditions. Since 2,3-dichloro-5~6-dicyanohydroquinone is converted to 2,3-dichloro-5,6-dicyanobenzoquinone by anodic oxidation during the reaction, the s-tarting catalyst can be either the benzoquinone, the hydroquinone or a mix-ture.
Since 2,3 dichloro-5,6-dicyanobenzoqu:inone is regenera-ted during the reaction, the catalys-t can he recovered and re-,,, ii~ ~ 3 --used. While it is necessary to use one mole of 2,3-dichloro-5,6-dicyanoben~oquinone in conventional chemical conversions, a catalytic amount can be employed in the practice of this invention. It is preferred to use Erom 2.5 to 10 weight percent of catalyst based on -the steroid weight.
The electrochemical clehydrogenation is advantageously conducted under basic conditions which adds to the stabi-lity of the enol ether under the reaction conditions.
Suitable bases v - 3a -employed in the present invention ~re insoluble or partially soluble bases which do not affect lactone chemistry. Pre-ferred bases are salts of alkali and alkaline earth metals such as sodium bicarbonate, sodium carbonate, lithium carbonate, calcium carbonate, magnesium carbonate and the like. Carbonates and bicarbonates are the preferred salts, although it will be apparent to those skilled in the art that other salts can be employed in this invention. The in-soluble or partially soluble bases are employed in amounts of between 25 percent to 50 percent by weight of steroid.
For optimum conditions, al: least 1 equivalent or 2 moles of base are employed.
Suitable electrolytes for use in the present invention are inert soluble salts which are stable to oxidation, such as the borates, chlorides, perchlorates, sulfonates, phos-phates and fluoroborates of lithium and tetraalkylammonium and the like, i.e., tetrabutylammoniumfluoroborate, tetra-ethylammonium ~luoroborate, lithium perchlorate, lithium chloride and the like. The electrolyte salts are employed in amounts of from about 5 percent to about 300 percent by weight of the steroid, preferably from about 10 percent to about 150 weight percent.
The solvent system employed in this invention is a partially aqueous polar organic solvent system, i.e., 10-50 percent aqueous acetonitrile, dimethylformamide, dioxane, nitromethane or other suitable high dielectric solvents.
The preferred anode material is carbon. Other suit-~ble anode materials include, but are not limited to, pla tinum and other suitable stable metal oxides such as PbO2, SnO2, TiO2 and the like.
The preferred cathode materials are platinum and stainless steel. ~lowever, a~y other low hydrogen overvol-t tage material -that evolves hydrogen from an aqueous elec-trolyte can be employed, i.e.~ rhuthenium, nickel and the like.
It is necessary to conduct -the reaction a-t suEficient applied voltage that current passes, the hydroquinone is oxidized and the desired product is obtained. The anode potential varies with the solvent, electrolyte, catalyst, pH and anode material.

~ 4a -,,~ .

The potential is determ.ined Lor a given ~ 3'5 enol ether sub-strate by cyclic voltammetry. The potential selected i5 such that the hydroquinone is oxidized but also such -that the substrate molecule is iner-t -to the anode, i.e., it does not react with the anode, in the absence oE the hydroqui-none. Generally, Eor the compounds used for illustra-tion purposes herein, a potential of up -to 1.5 V vs. Ag~AgNO3 is employed. In the case of a Ag/AgNO3 reference elec-trode, potentials of Erom -~0 -to 1.5 V are employed. The preferred potential is +0.7 V.
It will be understood by those skilled in the art that if a reference electrode other than Ag/AgNO3 is em-ployed, for example, standard calomel electrode (SCE), the applied potential would be adjusted accordingly, to, for example, between +0 to +1.2, pleferably about +0.4 V.
For optimal results, it is necessary to pulse the anode to a cathodic potential of not more than -0.5V for 3 seconds every 30 seconds.
It is wholly surprising that dehydrogenation with 2,3-dichloro-5,6--dicyanobenzoquinone can be effected under basic conditions since the preferred catalyst, as well as the other quinones are sensitive to base, and it is even more surprising that, using less quinone than is required by conventional chemical dehydrogenations, increased yields are obtained.
It has been found that the present process is par-ticularly advantageous for preparing 17-hydroxy-3-oxo-17-~i-pregna-4,6-diene-21 carboxylic acid ~lactone(17-N-(2-carboxyethyl-17~-hydroxyandros-ta-4,6-diene-3-one lactone, also known as canrenone (see The Merck Index, 9th edi-tion, page 222, No. 1750), U.S. Patent No. 2,900,383, :Erom the corresponding ~ 3)5 enol ether, 3-ethoxy-]7-hydroxy~17-N-- 5 ~

pregna-3,5-diene-21 carboxylic acid y-lac-tone. According-ly, the present invention is illustrated, in -the preferred embodiment, by -the preparation of 17-hydroxy-3-oxo-17-~-pregna-4,6-diene-21 carboxylic acid y-lactone and compared to standard 2,3-dichloro-5,6-dicyanobenzoquinone dehydro-genation of -the corre~ponding ~ 3~5 enol ether.

5a ---6~ ~ r~

Example 1 Preparation of 17-hydroxy-3-oxo-17-~-pregna-4,6-diene-21-carboxylic acid ~-lactone bv the elec-trochemical dehydrogenation of 3-ethoxy-17-hydroxy-17-~-pregna-3,5-diene-21-carboxylic acid-y-lactone using 2,3-dichloro-5,6-dicyanobenzoquinone as the catalyst ~

CH3CH20 a~lod~)

3-Ethoxy-17-hydroxy-17~-pregna-3,5-diene-21-carboxylic acid~-lactone~3.0 g, 8.1xlO 3mole), sodium bicarbonate(10.0 g, 1.2 x 10 2mole) and 2,3-dichloro~5,6-dicyanobenzoquinone(0.3 g, 1.2 x 10 3mole) ~ere placed in the anode compartment of a ~ cell along with a carbon rod bundle and a silver/silver nitrate reference electrode.
The electrolyte solution comprising acetonitrile(450 ml, lO.9mole), water(50 ml, 2.8mole) and tetraethylammonium-fluoroborate(ll.0 g, 5.0 x 10 2mole), was placed in the anode and cathode chamber along with a 6 cm x 2 cm plat-inum foil cathode. The potentiostat(P.A.R. model 173) was set to deliver ~0.7 V vs Ag/AgNO3 with pulsing to -0.500 V
Eor 1 second in every 20 secondsO The potentiostat was engaged and the initial current was 180 P~. The current decayed smoothly to 43 MA over a 5 hour period. Thin layer chromatography indicated the absence of the starting material and the presence of the desired product.
Sodium sulfite(5.0 g) was added and the mixture allowed to stir for 1 hour. The acetonitrile was removed on a rotary evaporator and the aqueous residue was extracted twice with 200 ml of ethyl acetate. The ethyl acetate extracts were dried over sodium sulfate, treated with activated carbon and evaporated to dryness to yield 2.8 g of the desired produc-t as yellow crys-tals. The product was obtained in approximately 93% purity and 93% yield. U.V.~
max=283, absorbance(l mg%) = 0.730, theoretical, 0.785. The product was identical to that obtained in U.S. Patent No.
2,900,3~3.

7 ~

Example 2 Preparation of 17-hydroxy-3-oxo-17-~-pre~na-

4,6-diene-21-carboxylic acid ~-lac-tone by elec-trochemical dehydrogenation with 2,3-di-chloro-5,6-dicyanobenzoquinone(DDQ) _ The electrochemical reaction of Example 1 was repeated exac-tly. The initial current was 160 MA and -the current de-cayed to 30 MA over a 3.5 hour period. Thin layer chromato-graphy indicated the absence of the starting enol ether and the presence of the desired product of 94.5% purity in 101~2%
yield.
Example 3 Preparation of 17-hydroxy-3-oxo-17-~-pregna-4,6-diene-21-carboxylic acid ~-lactone using 1 mole of DDQ by an analogous chemical conversion To 3-ethoxy-17-hydroxy-17-~-pregna-3,5-diene-21-carbox-ylic acid ~-lactone(3.0 g, 8.1 x 10 3 mole) in 440 ml of 10%
aqueous electrolyte solution prepared with acetonitrile(450 ml), water(50 ml), tetraethylammoniumfluoroborate(ll.0 g, 5.0 x 10 2 mole) and sodium bicarbonate(10.0 g, 1.2 x 10 1 mole), was added 2,3-dichloro-5,6-dicyanobenzoquinone(1.84 g, 8.1 x 10 mole) in 60 ml of the above electrolyte solu-tion. The addition was done over a 7 minute period and the reaction temperature went from 19 to 18.5C. No external cooling was used. The reaction was allowed -to stir for 5 hours and thin layer chromatography was conduc-ted at one hour intervals The reaction did not proceed after the first hour. After 5 hours, 1.02 g of sodium sulfite in 25 ml of water was added and the reaction allowed to stir for one additional hour.
The acetonitrile was removed on a rotary evaporator, and the residue diluted with 150 ml of additional water. The aqueous solution was extracted twice with 150 ml of ethyl acetate.
The organic extracts were washed with 150 ml of saturated po-tassium bicarbonate and sa-turated sodium chloride. The re-sulting crude product was dried over sodium sulfate, filter-ed, treated with activated charcoal and stripped -to yield 2.4 g of product as a glass in 86% crude yield and 53.4% yield oE
the desired product. U.V. ~max=283, absorbance(l mg %)= 0.49 theoretical=0.785. Purity of produc-t=0.49.0/0.785=62.4%.

Exa~le _ sy modifying the above procedure so that solid 2,3-dichloro-5~ 6-dicyanobenzoquinone in 170 mg portions was added a~ thirty minute interval~ during the irst ~ hours of a S 5 hour reaction time, 450 ml of acetonitrile and 50 ml of water bein~ initially present in the reaction mixture, 2.7 g o~ 88~ pure productt85% conversion) was obtained.
Example 5 By modifying the procedur~ o Example 3 so that 10 a S% aqueous acetonitrile solution was used in place of the 10% acetonitrile solution of Example 3, the desired product was obtained in 70.7% purity and 6~.2% yield ~s the'pure product~
(96.4% crude yield. U.V. ~max -283, absorbance(l mg%)-0.555, theoretical 0.785.
Example 6 By modifying the procedure of Example 1 so that about 80 mg of 2,3-dichloro-4,~-dicyanobenzoquinone(2.5 weig`ht percent of the starting steroid substrate) was used in place of ten weight pexcent of Example 1. The yield and product purity 20 was substantially identical with that obtained by the method of Example 1.
Example 7 Preparation of 17-~-acetoxy-3-ethoxy 11-~-methyl-19-norpre~-3,5-diene-20-one 17-a-Acetoxy~ -methyl l9-norpreg-4-ene 3,20-dione(5.0 g, 0.0134 mole, U.S~ Patent No. 3,527,778) was suspended in dioxane~50 ml), 2B ethanol(0.5 ml), and tri-ethylorthoformate(i.5 ml, 0.041 mole). ~-Toluenesulfonic acid monohydrate(0.25 g, 0.0013 mole) was dissolved in dioxane 30 (5 ml) and added to the stirred suspension under a nitrogen atmosphere. The dione slowly went into solution(about 1 hour), forming a yellow solution. The reac~ion mixture was stirred for two hours thereafter and pyridine ~5 ml) added. The solvents were evaporated on a rotary evaporator at 40C
- 35 and a water aspirator. The residue was dissolved in chloroform, washed three times with water, once with saturated sodium chloride solution, dried over sodi~m sulfate, filtered and stripped to yield 6.7 g of desired product.

,7~3 _9_ Example 8 Electrochemical conversion o 17-~-acetoxy-3-ethoxy~ -methyl-lg-norpre~-3,$-diene-20-one to 17-~-acetoxy-11-B methyl-19-norpreg-4,6-diene-3,20-dione 17--acetoxy-3-ethoxy~ -methyl-19-norpregn-3,S-diene-~0-one was electrochemically dehydrogenated to 17-~-acetoxy-11-~-methyl-19 norpreg~4,6-die~e-3,20-dione following the method of Example 1, using 6.7 g(O.Q134 mole~
10 of 3,5-diene, 500 ml of 10% aqueous acetonitrile (made 0.5 N, in tetxaethylam~oniumfluoroborate), 0.45 g (000018 mole~
of 2,3-dichloro-5,~-dicyanobenzoa~uinone, and 5 g of sodium ~icarbonate, using a carbon rod bundle anode with a :
silver/silver nitrate reference electrode and a stainless lS steel cathode in anH cell. The potentiosta~(P.A.R. model 173) - was set to deliver +0.5 V vs. Ag/AgNO3 wi~h pulsing to -.100 V
: for 3 seconds every 30 seconds.
At the conclusion of the reactionl about 1 g of sodium bisulfite was added ~nd the mixture was re~rigerated 20 ove~ night, diluted with water and extracted with ethyl acetate.
The e~yl acetate extract was washed twice with water, twice with 5% potassium carbonate, once with 10% sodium bisulfite, twice with water, once wi~h 5% sodium bisulfite, twice with water, once with !;% hydrochloric acid, twice with water, 25 and once with saturated sodium chloride, dri~d over sodium-sulfate and stripped to yield 5.8 g of product.
3O0 g of material was chromatographed on a column pac~ed with neutral alumina and eluted with an ethyl acetate-cyclohexane step aradient. The center cut was taken to pro~ide an ultra-30 pure sample for labelling purposes in approximately 40% yield,identical with that obtained in V.S. Patent No. 3,382~986.

Claims

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:-

1. An electrochemical process for dehydrogenating a steroidal .DELTA. 3,5 enol ether to provide the corresponding .DELTA. 4,6 dienone comprising the steps of reacting a steroidal .DELTA. 3,5 enol ether in the presence of a high potential catalyst, which is a quinone or the corresponding hydroquinone or a mixture thereof, under basic conditions, with a suitable electrolyte solution, at an applied voltage sufficient so that current passes, any hydroquinone present is oxidized, the .DELTA. 3,5 enol ether remains inert to the anode and the reac-tion proceeds to completion, and thereafter recovering the steroidal .DELTA. 4,6 dienone from the reaction mixture.

2. The process of claim 1. wherein said catalyst is employed in amount of from 2.5 to 10 percent by weight of said .DELTA. 3,5 enol.

3. The process of claim 1 wherein the electrolyte solution comprises an electrolyte selected from the group consisting of an inert soluble salt which is stable to oxidation, and a partially aqueous polar organic solvent system.

4. The process of claim 3 wherein the inert soluble salt is selected from the group consisting of the borate, chloride, perchlorate, sulfonate, phosphate and fluorobo-rate salts of lithium or tetraloweralkylammonium.

5. The process of claim 4 wherein the partially aqueous polar organic solvent system comprises a 10-50%
aqueous solution of a solvent selected from the group con-sisting of acetonitrile, dimethylformamide, dioxane and nitromethane.

6. The process of claim 1, 2 or 3 wherein said high potential catalyst is selected from the group consisting of 2,3-dichloro-5,6-dicyanobenzoquinone; 2,3-dichloro-5,6-dicyanvhydroquinone, or mixtures thereof, 3,3',5,5'-tetra-chloro-4,4'-diphenoquinone, tetrachloro-1,2-benzoquinone, and chloranil.

7. The process of claim 4 or 5 wherein said high potential catalyst is selected from the group consisting of 2,3-dichloro-5,6-dicyanobenzoquinone; 2,3-dichloro-5,6-dicyanohydroquinone, or mixtures thereof, 3,3',5,5'-tetra-chloro-4,4'-diphenoquinone, tetrachloro-1,2-benzoquinone, and chloranil.

8. The process of claim 1 wherein the reaction is carried out in a divided H cell.

9. The process of claim 8 wherein the anode is selected from the group consisting of carbon, platinum, lead oxide, tin oxide and titanium oxide and the cathode is selected from the group consisting of platinum, ruthe-nium, nickel, and stainless steel.

10. The process of claim 1, 2 or 3 wherein the base is selected from the group consisting of an alkali metal salt and an alkaline earth metal salt.

11. The process of claim 1, 2 or 3 wherein the base is selected from the group consisting of sodium bicarbonate, sodium carbonate, lithium carbonate, calcium carbonate and magnesium carbonate.

12. The process of claim 1, 2 or 3 wherein said cata-lyst is 2,3-dichloro-5,6-dicyanobenzoquinone.

13. The process of claim 1, 2 or 3 wherein said cata-lyst is selected from the group consisting of 2,3-dichloro-5,6-dicyanobenzoquinone, 2,3-dichloro-5,6-dicyanohydroqui-none and mixtures thereof.

14. The process of claim 1, 2 or 3 wherein the enol ether is a 19-nor-.DELTA. 3,5 enol ether.

15. An electrochemical process for dehydrogenating a steroidal .DELTA. 3,5 enol ether to provide the corresponding .DELTA. 4,6 dienone comprising the steps of reacting a steroidal A 3,5 enol ether in the presence of from about 2.5 to about 10 percent by weight of 2,3-dichloro-5,6-dicyanohydrobenzo-quinone under basic conditions with a suitable, partially aqueous electrolyte solution, for a period of from about 2 to about 5 hours at an applied voltage sufficient so that current passes, the 2,3-dichloro-5,6-dicyanohydro-quinone is oxidized, the enol ether remains inert to the anode and the reaction proceeds to completion, and there-after recovering the steroidal .DELTA. 4,6 dienone from the reac-tion mixture.

16. The process of claim 15 wherein said electrolyte solution comprises from 10 to 300 percent by weight of the enol ether of an inert soluble salt which is stable to oxi-dation, and an aqueous polar organic solvent system, said organic solvent containing 10 to 50% of water.

17. The process of claim 16 wherein said inert sol uble salt is selected from the group consisting of the bor-ates, chlorides, perchlorates, sulfonates, phosphates and fluoroborates of lithium or a tetraloweralkylammonium and the organic solvent is selected from the group consisting of acetonitrile, dimethylformamide, dioxane and nitromethane.

18. A method of preparing 17-hydroxy-3-oxo-17-.alpha.-preyna-4,6-diene-21-carboxylic acid .gamma.-lactone from a 3-alkoxy-17-hydroxy-17-.alpha.-pregna-3,5-diene-21-carboxylic acid .gamma.-lactone by electrochemical dehydrogenation comprising the steps of reacting said 3-alkoxy-17-hydroxy-17-.alpha.-pregna-3,5-diene-21-carboxylic acid .gamma.-lactone with from 2.5 to 10 weight percent of a high potential catalyst, which is a quinone or the cor-responding hydroquinone or a mixture thereof, under basic conditions, at an applied cell potential sufficient that cur-rent passes, any hydroquinone is oxidized and the 3,5-diene remains inert to the anode in the absence of phenol.

19. The method of claim 18 wherein said applied cell potential is +0 to 1.5 V vs. Ag/AgNO3.

20. The method of claim 18 wherein said applied cell potential is +0.7 V vs. Ag/AgNO3.

21. The method of claim 19 wherein said anode is pulsed to a cathodic potential of not more than -0.5 V for 3 seconds of every 30 seconds.

22. The method of claim 20 wherein said anode is pulsed to a cathodic potential of not more than -0.5 V for 3 seconds of every 30 seconds.

23. The method of claim 18, 19 or 20 wherein said cat-alyst is selected from the group consisting of 2,3-dichloro-5,6-dicyanobenzoquinone, 2,3-dichloro-5,6-dicyanohydroquinone or a mixture thereof.

24. The method of claim 18, 19 or 20 wherein said cat-alyst is 2,3-dichloro-5,6-dicyanobenzoquinone.

25. The method of claim 21 or 22 wherein said catalyst is selected from the group consisting of 2,3-dichloro-5,6-dicyanobenzoquinone, 2,3-dichloro-5,6-dicyano-hydroquinone or a mixture thereof.

26. The method of claim 21 or 22 wherein said cata-lyst is 2,3-dichloro-5,6-dicyanobenzoquinone.

27. The method of claim 18, 19 or 20 wherein the 3-alkoxy-.gamma.-lactone used as starting material is 3-ethoxy-17-hydroxy-17-.alpha.-pregna-3,5-diene-21-carboxylic acid .gamma.-lactone

28. The method of claim 21 or 22 wherein the 3-alkoxy-y-lactone used as starting material is 3-ethoxy-17-hydroxy-17-.alpha.-pregna-3,5-diene-21-carboxylic acid .gamma.-lactone

29. The method of claim 18, 19 or 20 wherein the 3-alkoxy-.gamma.-lactone used as starting material is 3-ethoxy-17-hydroxy-17-.alpha.-pregna-3,5-diene-21-carboxylic acid .gamma.-lactone and the catalyst is selected from the group consisting of 2,3-dichloro-5,6-dicyanobenzoquinone, 2,3-dichloro-5,6-dicyanohydroquinone or a mixture thereof.

30. The method of claim 21 or 22 wherein the 3-alkoxy-.gamma.-lactone used as starting material is 3-ethoxy-17-hydroxy-17-.alpha.-pregna-3,5-diene-21-carboxylic acid .gamma.-lactone and the catalyst is selected from the group consisting of 2,3-dichloro-5,6-dicyanobenzoquinone, 2,3-dichloro-5,6-dicyanohydroquinone or a mixture thereof.

31. The method of claim 18, 19 or 20 wherein the 3-alkoxy-.gamma.-lactone used as starting material is 3-ethoxy-17-hydroxy-17-.alpha.-pregna-3,5-diene-21-carboxylic acid .gamma.-lactone and the catalyst is 2,3-dichloro-5,6-dicyanobenzoquinone.

32. The method of claim 21 or 22 wherein the 3-alkoxy-.gamma.-lactone used as starting material is 3-ethoxy-17-hydroxy-17-.alpha.-pregna-3,5-diene-2l-carboxylic acid .gamma.-lactone and the catalyst is 2,3-dichloro-5,6-dicyanobenzoquinone.